The gut microbiota is a complex ecosystem defined by the combination of microorganisms living in the gastrointestinal tract. Its equilibrium is intimately involved in several aspects of vital process for human physiology and nutrition. Its composition changes depending on both exogenous and endogenous factors. The disruption of the gut microbiota by antibiotics often leads to an opportunistic infection by Clostridium difficile. The unbalanced intestinal microbiota promotes spore germination, growth of vegetative forms and toxin production leading to C. difficile infection, which is characterized by diarrhea and possibly pseudomembranous colitis. This nosocomial infection is a good model to understand the role of the gut microbiota in preventing the development of pathogens.
BackgroundRapid commercial assays, including nucleic acid amplification tests and immunoassays for Clostridium. difficile toxins, have replaced the use of older assays. They are included in a two-step algorithm diagnosis, including first the detection of the glutamate dehydrogenase (GDH) as a screening method and second the detection of toxins as a confirmatory method. Although assays that detect the presence of free toxins in feces are known to lack sensitivity, they are preferable to confirm infection. We evaluated the accuracy of the chemiluminescence-based method detecting C.difficile GDH and free toxins A/B (DiaSorin algorithm) to an enzyme-immunoassay (EIA) for GDH with a molecular toxins test (Meridian algorithm), EIA-GDH and an EIA-toxins A/B algorithm (Alere algorithm) with and without toxigenic culture for confirmation.FindingsA total of 468 diarrhoeal and loose stool samples were included in the study. A positive result was defined by a positive GDH and a positive toxin test. Discordant samples were resolved using an enriched toxigenic culture considered as the reference method. After resolution, the DiaSorin algorithm showed a high sensitivity (86.7 %) compared to that of the Alere algorithm with (60.0 %) and without (50.0 %) confirmation by culture and was as sensitive as the Meridian algorithm (90.0 %), while the specificities were similar: 99.1, 99.5, 99.5 and 98.9 %, respectively.ConclusionsThe DiaSorin algorithm was as sensitive as an algorithm including nucleic acid amplification test for toxins. Chemiluminescence toxin-enhanced signal assay compensates the lack of sensitivity usually observed for EIA tests for toxins.
To the editor Soft-tissue sarcomas (STS) represent a very heterogeneous group of rare tumors including more than 100 different subtypes [1]. Surgery and neo/adjuvant radiation therapy represent the cornerstone of treatment for STS. However, despite an optimal resection of the tumor, up to 40% of patients will develop metastatic relapse and will die from the disease [1]. Doxorubicin represents the first-line standard of care for patients with advanced disease since the 1970s, despite several attempts to identify better regimens. The median overall survival (OS) of patients with metastatic disease is < 18 months and has only modestly improved over the past 20 years [2].We and others have previously reported that nextgeneration sequencing (NGS) of tumor tissues allows the identification of genomic aberrations with the potential to influence and personalize therapy in up to 50% of patients with advanced STS [3,4].Genomic profiling of circulating tumor DNA (ctDNA) is increasingly used to tailor therapy in cancer patients. Indeed, such liquid biopsy has several advantages: noninvasiveness, reduced turnaround times for faster results, and the ability to fully capture the landscape of tumor heterogeneity [5].The aims of the present study were to investigate the impact of ctDNA profiling in a large cohort of patients with advanced STS included in two prospective precision medicine studies and to decipher the ctDNA molecular landscape of sarcoma.
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